P1220: CHARACTERISTICS OF SECONDARY CENTRAL NERVOUS SYSTEM INVOLVEMENT IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA – A SUPPLEMENTARY ANALYSIS OF JCOG0601
Authors: K. Shimada, K. Ohmachi, R. Machida, S. Ota, H. Itamura, H. Tsujimura, N. Takayama, T. Shimada, M. Kurosawa, T. Tabayashi, T. Shimoyama, K. Ohshima, D. Maruyama, T. Kinoshita, K. Ando, T. Hotta, K. Tsukasaki, H. Nagai
Journal: HemaSphere (2022)

Background: Secondary central nervous system involvement (sCNSi) during the clinical course of diffuse large B-cell lymphoma (DLBCL) develops in approximately 5% of patients, and has a poor prognosis. The features of sCNSi in patients identified as higher risk according to international prognostic index (IPI) and CNS-IPI have been well evaluated, however those in patients with sCNSi who are lower risk by IPI or CNS-IPI are not yet fully understood. Aims: To explore the characteristics of sCNSi in patients who participated in JCOG0601 and were considered mainly low risk according to IPI. Methods: Of 409 eligible patients in the JCOG0601 randomized controlled trial, we evaluated patients who developed sCNSi at their first progression. The JCOG0601 trial compared standard R-CHOP-21 (arm A, n = 204) and RW-CHOP-21 in which rituximab is administered 8 times per week from the commencement of treatment (arm B, n = 205) for untreated patients with DLBCL (Ohmachi K, et al. Blood Adv. 2021;5:984). Patients were grouped according to IPI as follows: in arm A, 92 in lower risk (L), 67 in low-intermediate risk (L-I), 33 in high-intermediate risk (H-I), and 15 in high risk (H); in arm B, 112 in L, 67 in L-I, 18 in H-I, and 8 in H. Patients at lower risk of IPI accounted for 82% of the total. The risk of CNS-IPI in each arm was as follows: in arm A, 91 in L, 96 in intermediate (I), and 17 in H; in arm B, 112 in L, 84 in I, and 9 in H. The protocol did not allow CNS prophylaxis. The cumulative incidence (CI) of sCNSi was calculated with consideration to competing risks of death and non-CNS progression or relapse. Results: Median follow-up was 4.9 years, during which 21 patients (5.1%) developed sCNSi. The 5-year overall CI of sCNSi was 5.1%, and that in L, I, and H of CNS-IPI was 4.0%, 5.3%, and 11.5%, respectively. Five-year CI of sCNSi was 7.3% in arm A and 2.9% in arm B (Gray’s test, p = 0.11). The CI of sCNSi by CNS-IPI was 5.6% in L, 6.8% in I, and 17.6% in H in arm A; and 2.7% in L, 3.6% in I, and 0% in H in arm B. Of the 21 patients with sCNSi, 8, 10, and 3 were categorized as L, I, and H of CNS-IPI, respectively. Common locations of extranodal lesions at the time of registration in patients with sCNSi were stomach (n = 4), paranasal cavity (n = 3), and bone marrow (n = 2). In particular, 2 of 3 patients with paranasal cavity lesions were categorized as L or I of CNS-IPI. In univariable analysis, paranasal cavity lesion was a high-risk factor for sCNSi (subdistribution hazard ratio, 4.34 [95% confidence interval, 1.28–14.73], p = 0.018). Kidney and adrenal gland, which are high-risk organs in CNS-IPI, were not high risk in this analysis. Median overall survival (OS) after sCNSi was 1.3 years, with 2-year OS of 39.3%. Summary/Conclusion: sCNSi in DLBCL patients at lower risk of CNS-IPI was low, as previously reported, but those with paranasal cavity lesions developed sCNSi despite the lower risk of CNS-IPI.